Dissecting the Functional Heterogeneity of Pearson Syndrome via Single Cell Sequencing

Overview

Computational Biologist, Harvard University Dr. Vijay Sankaran Principle Faculty, Harvard Stem Cell Institute Research Science Institute Pearson Syndrome is a rare, multisystemic genetic condition caused by large deletions of mitochondrial DNA (mtDNA), typically resulting in sideroblastic anemia and exocrine pancreatic dysfunction. While some of the phenotypic characterizations of Pearson have been defined, there is little to no understanding of the specific genetic or molecular basis underlying disease pathogenesis. Here, we hypothesized that utilizing a single cell genomics approach would facilitate the inference of the etiology of this condition. In particular, by leveraging the naturally- occurring heteroplasmic variation between cells, we sought to identify molecular mediators of Pearson Syndrome . By analyzing single-cell ATAC-seq and RNA-seq data of various patient-derived cell lines, we identified a set of 10 genes associated with Pearson Syndrome pathogenesis across sample sets. Further, more comprehensive associations further defined molecular pathways potentially involved in Pearson Syndrome development, including angiogenesis, extracellular adhesion, and protein binding. Overall, this work demonstrates the utility of single -cell genomics approaches to understand rare, Mendelian disorders in uncovering a molecular basis of disease. Further, our results show how synthesizing multiple modes of information across multiple single-cell technologies and analytical tools can potentially enhance diagnostics and therapeutics for rare diseases like Pearson Syndrome. The Variability Hypothesis and Distribution of Standardized Test Scores Irene Mamontov Farragut High School Farragut, Tennessee The current study uses the SAT® test scores distributions for the years of 2012, 2013, 2014, and 2015 to explore the greater male variability hypothesis, which postulates that, due to the greater variability in cognitive aptitude, males are expected to outnumber females at both the lower and upper tails of the standardized test scores distribution. While the SAT® test scores indeed show male-to-female ratios greater than one at the lower and upper tails of the score distributions, the current study demonstrates that the customarily employed assumption of the normal distribution of the test scores overestimates the male-to-female ratio at the upper tail. Furthermore, extrapolation of the normal score distribution model beyond the upper test score cutoff predicts a large male -to- female ratio for the individuals of the very high cognitive aptitude that cannot be assessed by the standardized tests. However, a modified model comprising two normal distribution components, which provides an accurate description of the actual score distributions at the tails, predicts an approximately 1:1 male-to-female representation up to 4.5 standard deviations above the mean cognitive aptitude. Thus, the results of the current study caution against the use of the customarily employed assumption of the normal distribution of the test scores for validating the greater male variability hypothesis and comparing the cognitive aptitude of males and females, especially near and beyond the upper score cutoff.

Competition history

• JSHS 2020 Category not listed

Resources

• National JSHS abstract book ↗

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